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==LarC2, the C-terminal domain of a cyclometallase involved in the synthesis of the NPN cofactor of lactate racemase, in complex with MnCTP==
<StructureSection load='6bwq' size='340' side='right'caption='[[6bwq]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bwq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lactiplantibacillus_plantarum Lactiplantibacillus plantarum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BWQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BWQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bwq OCA], [https://pdbe.org/6bwq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bwq RCSB], [https://www.ebi.ac.uk/pdbsum/6bwq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bwq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LARC_LACPL LARC_LACPL] Involved in the biosynthesis of a nickel-pincer cofactor ((SCS)Ni(II) pincer complex). Binds Ni(2+), and functions in nickel delivery to pyridinium-3,5-bisthiocarboxylic acid mononucleotide (P2TMN), to form the mature cofactor. Is required for the activation of the lactate racemase LarA. May also be involved in the activation of other nickel-pincer cofactor-dependent enzymes.<ref>PMID:24710389</ref> <ref>PMID:27114550</ref> 
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== Publication Abstract from PubMed ==
Bacterial lactate racemase is a nickel-dependent enzyme that contains a cofactor, nickel pyridinium-3,5-bisthiocarboxylic acid mononucleotide, hereafter named nickel-pincer nucleotide (NPN). The LarC enzyme from the bacterium Lactobacillus plantarum participates in NPN biosynthesis by inserting nickel ion into pyridinium-3,5-bisthiocarboxylic acid mononucleotide,. This reaction, known in organometallic chemistry as a cyclometalation, is characterized by the formation of new metal-carbon and metal-sulfur sigma bonds. LarC is therefore the first cyclometallase identified in nature, but the molecular mechanism of LarC-catalyzed cylometalation is unknown. Here, we show that LarC activity requires Mn(2+)-dependent CTP hydrolysis. The crystal structure of the C-terminal domain of LarC at 1.85 A resolution revealed a hexameric ferredoxin-like fold and an unprecedented CTP binding pocket. The loss of function of LarC variants with alanine variants of acidic residues lead us to propose a carboxylate-assisted mechanism for nickel insertion. This works also demonstrates the in vitro synthesis and purification of the NPN cofactor, opening new opportunities for the study of this intriguing cofactor and of NPN-utilizing enzymes.

Biosynthesis of the nickel-pincer nucleotide cofactor of lactate racemase requires a CTP-dependent cyclometallase.,Desguin B, Fellner M, Riant O, Hu J, Hausinger R, Hols P, Soumillion P J Biol Chem. 2018 Jun 10. pii: RA118.003741. doi: 10.1074/jbc.RA118.003741. PMID:29887527<ref>PMID:29887527</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6bwq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Lactiplantibacillus plantarum]]
[[Category: Large Structures]]
[[Category: Fellner M]]
[[Category: Hausinger RP]]
[[Category: Hu J]]